Genomic DNA in cells in which all the information necessary for the maintenance of life is written is always undergoing damage caused by various exogenous and endogenous factors. As exogenous factors, ultraviolet light, ionizing radiation and environmental chemical substances may be enumerated, for example. As endogenous factors, several types of active oxygen generated from energy metabolism and oxidation stress may be enumerated, for example. Further, mismatches that do not pair correctly with the template can be generated during DNA replication.
When these damaged sites or mismatches are left without repair, bases in the relevant sites will be different from what they are supposed to be, resulting in inaccurate genetic information, i.e., mutations. If a mutation has occurred in a coding region for a protein, the protein may have lower activity (or even no activity) than the corresponding native protein, or the protein may not be produced at all. If a mutation has occurred in a regulatory region, the level of synthesis of the protein under the control of this region can be abnormally increased or decreased. Further, control by other proteins may become ineffective. These changes may cause apoptosis or abnormal growth, e.g., canceration, in relevant cells.
Since damages or mismatches in DNA affect the life of cells per se and may even affect the life of the individuals to which the cells belong, cells have mechanisms to repair DNA damages or mismatches and thereby to maintain genetic information accurately. These are called DNA repair mechanisms. There are several types of DNA repair mechanisms, including base excision repair, photoreactivation, nucleotide excision repair, mismatch repair and recombination repair. It is expected that elucidation of DNA repair mechanisms would provide findings useful for the study of diseases such as cancer and the study of effects of environmental factors on living organisms. Furthermore, certain types of proteins involved in DNA repair mechanisms are expected to increase the accuracy of PCR that has become an important technique in various fields beyond the field of molecular biology.
Genes of a number of DNA repair enzymes have already been cloned from various organisms, and three-dimensional structural analysis of proteins has been carried out for some of them. However, most of these studies performed to date are genetic studies, and biochemical studies have been performed little. In order to elucidate DNA repair mechanisms and obtain findings useful in various fields such as medicine, it is necessary to clone all genes involved in DNA repair and to carry out three-dimensional structural analysis and detailed functional analysis of the encoded proteins.